Evaluation of Plasma Isoprostane in Patients with Oral Lichen Planus.

STATEMENT OF THE PROBLEMS
Lichen planus is a chronic inﬂammatory disease. Free radicals and reactive oxygen species play important roles in pathogenesis of oral lichen planus (OLP). Isoprostanes show oxidative stress and are formed by free-radical mediated lipid peroxidation of arachidonic acid and cell membrane phospholipids.


PURPOSE
This study was conducted to evaluate the plasma level of 8-isoprostane in patients suffering from erosive and non-erosive forms of OLP.


MATERIALS AND METHOD
In this case-control study, 31 patients with OLP and 30 control subjects were enrolled. Plasma samples were obtained and the level of 8-isoprostane was measured with Sandwich enzyme-linked immunosorbent assay (ELISA) in both groups. The data were analyzed by using two-sample t-test, chi-square and ANOVA tests.


RESULTS
The results showed significant increase in the plasma level of 8-isoprostane in OLP group compared with the control group. The results of independent t-test revealed no significant correlation between the plasma level of isoprostane and sex, smoking, or previous treatment.


CONCLUSION
Based on the findings of this study, oxidative stress was increased in patients with OLP, reflected by higher concentrations of 8-isoprostane in plasma.


Introduction
Lichen planus is a chronic inflammatory disease [1][2] and common dermatological condition that affects the oral cavity and skin with a prevalence of 1-2% in the general population. [3] Oral lichen planus (OLP) affects the oral mucosa of white females over 40 years old more than others. [4] It has various forms of clinical manifestations such as keratotic, atrophic, bullous, and erosive (ulcerative) lesions that may affect various sites of oral cavity. [5][6] Although the etiology and pathogenesis of OLP is not well-determined, genetic predisposition, stresses, as well as some of viral and bacterial agents are various fa-ctors that may act as risk factors for this disease. [7][8][9][10] The etiology of OLP has become more evident during the recent years and the immune system is proposed to have a primary role in the development of this disease. This theory is supported by the histopathologic characteristics of a subepithelial band-formed infiltrate dominated by T-lymphocytes and macrophages. [5] On the other hand, it is hypothesized that free radicals and reactive oxygen species (ROS) also have strong relationship with OLP pathogenesis and carcinogenesis. [11] It should be considered that in the histopathologic evaluation of lichen planus, basal cell degeneration, infiltration of inflammatory cells (like T-lymphocytes), and destruction of keratinocytes are observed. [12] Free radicals and the other active oxygen compounds intensify the inflammatory reactions in the presence of T-lymphocytes and destroy the lipid membrane of keratinocytes. [13][14] Free radicals are able to produce chemical modifications and damage the proteins, lipids, and nucleotides. Reactive free radicals may damage cells by starting lipid peroxidation that causes deep changes in the structural integrity and functions of cell membranes.
[15] The role of stress oxidative indices has been introduced in many autoimmune and inflammatory diseases such as atopic dermatitis, psoriasis vulgaris, vitiligo, and dermal lichen planus. The effect of stress oxidative indices in the pathophysiologic changes occurred in the basal cell of epidermis and they verified the decreased antioxidants defense and an increased oxidative damage to the lipids, DNA and proteins. [16][17] F2-isoprostanes are a group of bioactive prostaglandins produced by oxidative catalyzed reaction of arachidonic acid. They are discussed as the reliable marker of lipid peroxidation in vivo. [18] Isoprostanes can be released into the blood circulation, body secretions and urine. [19] Elevated levels of plasma and/or urinary 8-isoprostane have been reported in several conditions such as diabetes, [20][21] alcoholic liver diseases, and cardiovascular diseases. [22][23] 8isoprostane has been proposed as a reliable biomarker of oxidative stress and antioxidant deficiency because of its biochemical stability. [24] The aim of this study was to evaluate the isoprostane plasma level in patients suffering from erosive and keratotic OLP in comparison with the control healthy group.

Materials and Method
In this case-control study, 31 participants with consecutive OLP, including 20 females and 11 males were en- The collected data was analyzed by using SPSS software, version 11.5 (Chicago; IL). Two-sample t-test, chi-square, and ANOVA were used as appropriated. P-value<0.05 was deliberated as the statistical significance in this study.

Results
In this study, OLP was classified as non-erosive (reticul- The achieved results showed a significant increase in the plasma level of 8-isoprostane in OLP group compared with the control group (Table 1).
Comparing the erosive and non-erosive OLP revealed the isoprostane plasma level in erosive OLP group was significantly higher than keratotic OLP (p< 0.001) ( Table 2). [15, [25][26] Other studies pointed out the impact of stress oxidative indices on the pathophysiologic changes occurred in the basal cells of epidermis and concluded a de-creased antioxidant defense and an increased oxidative damage to the lipids, proteins and DNA molecules in patients suffering from OLP. [16,27] It was found that ROS produced by keratinocytes, fibroblasts and various inflammatory cells could result in disequilibrium between the pro-oxidants and antioxidants. [28] Reactive oxygen metabolites destruct the cell membranes by lipid peroxidation. [29] Researchers have proven the role of oxidative In another study conducted on 45 patients with lichen planus and 45 control individuals in Egypt, the serum level of NO increased substantially. [16] Payeras et al. found low levels of uric acid and significantly higher MDA levels in saliva of OLP patients compared with the control group. In serum, however, gamma-glutamyl transferase (GGT) was higher and total antioxidant defense was lower in OLP patients than those in healthy subjects. [31] Isoprostanes, isomers of PGF2α, emerged as one of the most accurate approaches to assess oxidant injury in vivo. [32] The discovery of isoprostanes had important implications in medicine. Namely, measurement of F2isoprostanes provides an important tool to explore the role of oxidative stress in the pathogenesis of human disease; thus, it is the most reliable approach to assess oxidative stress status in vivo. In addition, the products of isoprostane pathway have been found to exert potent biological actions and therefore may be pathophysiologic mediators of the disease. [33] In fact, in the Biomarkers of Oxidative Stress stu- investigating the pathophysiology of oxidative injury.
[33] It is suggested that measurement of F2-isoprostanes may provide a uniquely valuable approach to determine whether improvement of oxidative stress mitigates the manifestations of diseases or not. [33] Further studies are suggested to assess the markers of oxidative stress before and after the treatment in these cases.

Conclusion
This study showed significant increase in the plasma level of 8-isoprostane in patients with OLP compared with the control group, supporting the hypothesis that oxidative stress may be a potential target for developing new strategies of drug treatments.
Based on the achieved findings, measurement of F2-isoprostanes provides investigators with a unique tool to assess the role of free radicals in the pathogenesis of lichen planus with a degree of reliability that were not possible before. Further studies with larger sample sizes are required to realize the role of 8-Isoprostane and other oxidative stress indices in oral mucosal diseases thoroughly.